Major depression occurs with high prevalence in women 30-44 years of age-- the same age period during which changes in ovarian physiology are occurring. In a recently completed population-based case-control study, we observed a significant association between self-reported history of medically treated depression and increased risk of early menopause. These observations raise the question of whether major depression is a manifestation of declining ovarian function that precedes the cessation of periods, or whether major depression, or its therapy, is a precursor and potential risk factor for declining ovarian function. An epidemiologic study is proposed to confirm and define the nature of the relationship between major depression and changes in ovarian function. Approximately 12,000 women between 40-44 years of age will be surveyed in the greater Boston area to identify a cohort of 1,200 premenopausal women, 300 of whom have a past or current history of major depression and 900 of whom have no current or past history of major depression. Current and past history of major depression will be determined with the use of the CES-D depression inventory, and then verified using telephone and inperson SCID-P psychiatric assessments. All cohort members will provide baseline early follicular phase blood donations for FSH and estradiol and participate in psychosocial, reproductive and medical interviews. Prospective followup every 6 months for a period of 3 years will include menstrually timed blood donations, and followup questionnaires to assess onset and offset of depressive episodes, intervening negative life events, changes or introduction of pharmacotherapy, and menstrual history changes. Data from this cohort will be analyzed using logistic regression methods and Cox proportional hazards modelling, to test three hypotheses: 1) major depression is a precursor and risk factor for declining ovarian function, 2) pharmacological treatment for major depression is a precursor and risk factor for declining ovarian function, and 3) declining ovarian function precedes and possibly causes major depression. We will also determine whether number of prior episodes of depression are associated with baseline levels of FSH, and whether changes in FSH are predictive of recurrent depressive episodes. Since women in their late reproductive years have the highest rates of major depression, and close to 40% of women suffering from depression fail to seek psychiatric help, depression is a major public health problem in terms of suffering and foregone earnings. Understanding the relationship between major depression and declining ovarian function may help to provide meaningful avenues of intervention.